Expression of Ciliary Neurotrophic Factor and the Neurotrophins – Nerve Growth Factor, Brain‐Derived Neurotrophic Factor and Neurotrophin 3—in Cultured Rat Hippocampal Astrocytes

Abstract

Cultured astrocytes are known to possess a range of neurotrophic activities in culture. In order to examine which factors may be responsible for these activities, we have examined the expression of the genes for four known neurotrophic factors-ciliary neurotrophic factor (CNTF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3)-in purified astrocyte cultures derived from neonatal rat hippocampus. Hippocampal astrocytes were found to express mRNA for three neurotrophic factors-CNTF, NGF and NT3-at significantly higher levels than other cultured cell types or cell lines examined. BDNF messenger RNA (mRNA), however, was undetectable in these astrocytes. The levels of CNTF, NGF and NT3 mRNA in astrocytes were largely unaffected by their degree of confluency, while serum removal caused only a transient decrease in mRNA levels, which returned to basal levels within 48 h. Astrocyte-derived CNTF was found to comigrate with recombinant rat CNTF at 23 kD on a Western blot. Immunocytochemical analysis revealed strong CNTF immunoreactivity in the cytoplasm of astrocytes, weak staining in the nucleus, but no CNTF at the cell surface. NGF and NT3 were undetectable immunocytochemically. CNTF-like activity, as assessed by bioassay on ciliary ganglion neurons, was found in the extract of cultured astrocytes but not in conditioned medium, whereas astrocyte-conditioned medium supported survival of dorsal root ganglion neurons but not ciliary or nodose ganglion neurons. This conditioned medium activity was neutralized with antibodies to NGF. Astrocyte extract also supported survival of dorsal root ganglion and nodose ganglion neurons, but these activities were not blocked by anti-NGF. Part, but not all, of the activity in astrocyte extracts which sustained nodose ganglion neurons could be attributed to CNTF.

Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain

“…4,6 Astrocytes are located close to the neural stem cells in the adult dentate gyrus 54 and can express several factors that are able to independently increase proliferation. 55,56 Of particular relevance to the present study is the clear connection found between astrocytes, learning and PKCg. 57 Thus, this suggests the mechanism for behavioral reversal, given the well-known connection between PKCg and Morris maze performance.…”

Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice

“…The chemokines secreted by MSCs may have acted directly on the NSCs. However, it is also possible that factors secreted by the MSCs activated nearby astrocytes and activation of the astrocytes produced the increase in neurogenesis, because astrocytes are located in close proximity to NSCs (6) in the hippocampus and express several factors that independently increase neurogenesis (36,37).…”

Neurotrophin signaling among neurons and glia during formation of tripartite synapses

“…Several groups have reported that primary astrocytes in culture produce NGF, BDNF and NT 3 , and that the expression of these neurotrophins and their receptors in astrocytes is modulated by cAMP signaling (Furukawa et al, 1987;Houlgatte et al, 1989;Rudge et al, 1992;Condorelli et al, 1994). Thus, astrocytes might release neurotrophins that affect neurons that, in turn, enhance synapse formation and function.…”